Recent trends of cancer in Europe: A combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s

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1 E U RO P E A N J O U R NA L O F CA N C E Rxxx (2008) xxx xxx available at journal homepage: Recent trs of cancer in : A combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s Henrike E. Karim-Kos a, *,1, Esther de Vries a,1, Isabelle Soerjomataram a, Valery Lemmens a,b, Sabine Siesling c, Jan Willem W. Coebergh a,b a Department of Public Health, Erasmus MC University Medical Centre Rotterdam, Room: AE-107, P.O. Box 2040, 3000 CA Rotterdam, Netherlands b Eindhoven Cancer Registry, Comprehensive Cancer Centre South, Eindhoven c Comprehensive Cancer Centre Stedriehoek Twente, Enschede ARTICLE INFO ABSTRACT Article history: Received 21 November 2007 Accepted 17 December 2007 Keywords: Cancer registry Incidence Mortality Neoplasm Survival Trs Introduction: We present a comprehensive overview of most recent an trs in population-based incidence of, mortality from and relative survival for patients with cancer since the mid 1990s. Methods: Data on incidence, mortality and 5-year relative survival from the mid 1990s to early 2000 for the cancers of the oral cavity and pharynx, oesophagus, stomach, colorectum, pancreas, larynx, lung, skin melanoma, breast, cervix, corpus uteri, ovary, prostate, testis, kidney, bladder, and Hodgkin s disease were obtained from cancer registries from 21 an countries. Estimated annual percentages change in incidence and mortality were calculated. Survival trs were analyzed by calculating the relative difference in 5-year relative survival between and using data from EUROCARE-3 and -4. Results: Trs in incidence were generally favorable in the more prosperous countries from Northern and Western, except for obesity related cancers. Whereas incidence of and mortality from tobacco-related cancers decreased for males in Northern, Western and Southern, they increased for both sexes in Central and for females nearly everywhere in. Survival rates generally improved, mostly due to better access to specialized diagnostics, staging and treatment. Marked effects of organised or opportunistic screening became visible for breast, prostate and melanoma in the wealthier countries. Mortality trs were generally favourable, except for smoking related cancers. Conclusion: Cancer prevention and management in is moving in the right direction. Survival increased and mortality decreased through the combination of earlier detection, better access to care and improved treatment. Still, cancer prevention efforts have much to attain, especially in the domain of female smoking prevalence and the emerging obesity epidemic. Ó 2007 Elsevier Ltd. All rights reserved. * Corresponding author: Tel.: ; fax: address: h.karim@erasmusmc.nl (H.E. Karim-Kos). 1 Both authors contributed equally to the manuscript /$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi: /j.ejca Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J

2 2 E U R O P E A N J O U R N A L O F CA N C E Rxxx (2008) xxx xxx 1. Introduction Cancer has become a major public health problem in with an estimated prevalence of about 3%, increasing to 15% at old age. Almost 50% of deaths at middle age is caused by cancer, partly resulting from lowering mortality from other causes of death. In 2002, 26% of all cancer cases in the world were diagnosed in. 1 Figs. 1 and 2 show the distribution of estimated cancer incidence and mortality for 2006; breast, colorectal, prostate and lung cancers were the most important cancer types in. 2 The progress against cancer is often focussed on survival of individual cancer patients. The recent paper on trs in survival of cancer across up to 2002 by the EUROCARE group clearly showed that the most marked improvements occurred among patients with colorectal, breast, prostate and thyroid cancer and lymphomas, both Hodgkin s and non-hodgkin s. 3 Little explicit clarification was given for the observed differences between the countries. These differences may be due to variation in the baseline characteristics of the covered populations, e.g. selective areas in a country or state with large proportions of inhabitants having a high Males Females Oral cavity, pharynx 5% Oesophagus 2% Oral cavity, pharynx 2% Oesophagus 1% Stomach 4% Other 31% Stomach 6% Colorectum 13% Other 32% Colorectum 13% Larynx 0% Larynx 3% Lung 6% Leukaemia 3% Prostate 20% Lung 17% Leukaemia 3% Uterus 10% Breast 29% Fig. 1 Distribution of new cancer cases in by ger, 2006 Source: Ferlay et al. 2 Other 34% Males Oral cavity and Pharynx 4% Oesophagus 3% Stomach 7% Colorectum 11% Larynx 2% Oral cavity and Pharynx 1% Other 41% Females Oesophagus 1% Stomach 6% Colorectum 13% Larynx 0% Lung 11% Leukaemia 3% Prostate 9% Lung 27% Leukaemia 3% Uterus 6% Breast 18% Fig. 2 Distribution of cancer deaths in by ger, 2006 Source: Ferlay et al. 2 Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J

3 E U RO P E A N J O U R NA L O F CA N C E Rxxx (2008) xxx xxx 3 Table 1 Possible explanations for combined changes in trs in incidence of, survival for and mortality from cancer Incidence Survival Mortality Plausible explanation(s) for changes " " " Higher prevalence of risk factors, earlier diagnosis and/or shifts to unfavourable subsites/-types. If incidence increased faster than survival, mortality rates also increase. " " = Artificial increases in incidence due to e.g. screening, leading to increased survival rates due to lead-time bias, but not resulting in any changes in mortality. Higher prevalence of risk factors, favourable shifts in stage-distribution and/or subsites/-types and/or improved treatment. The net result is no changes in mortality. " " # Artificial increase in incidence due to e.g. screening, increased survival due to favourable shifts in stage-distribution and/or subsites/-types and effective early treatment, resulting in decreasing mortality after 5 10 years. " = " Higher prevalence of risk factors for aggressive tumours " # " Higher prevalence of risk factors, unfavourable shifts in stagedistribution and/or subsites/-types. = " # Improved treatment = = = No changes = # " Worsening case-mix, e.g. when screening manages to detect most if not all slow growing tumours # " # Lower risk factor prevalence and/or pre-malignant screening, more favourable case-mix and/or better staging or treatment # = # Lower risk factor prevalence and/or more restrictive classification and/ or pre-malignant screening without changes in survival will result in decreasing mortality rates # # = Lower risk factor prevalence and/or more restrictive classification, resulting in worsening survival All other combinations of incidence, survival mortality trs Probably registrion artefacts or problems (e.g. missing cases, incomplete follow-up, coding errors). socio-economic status. Other explanations are the potentially selective incompleteness of cases at time of detection or diagnosis and during follow-up. In the US, survival improvements were also revealed and largely determined by marked improvements in detection, thereby introducing lead-time and length bias, together with shifts in classification, subtype, and subsite resulting in pseudo-improvements of survival rates. 4 To circumvent these problems, it is preferred to study simultaneously trs in cancer incidence and survival, also because both affect mortality. 5,6 Survival improvements are more often preceded by rises in incidence than followed by decreases in mortality. Table 1 summarises possible explanations for changes in incidence, survival, and mortality. In this article we present the most recent trs in incidence, mortality, and survival over the last decade across of 17 tumour sites, derived from cancer registries and mortality statistics. 2. Methods Data of the following 17 tumour sites (and corresponding ICD- 10 code) were collected: oral cavity and pharynx (C00-14), oesophagus (C15), stomach (C16), colorectal (C18-21), pancreas (C25), larynx (C32), lung (C33-34), skin melanoma (C43), female breast (C50), cervix (C53), corpus uteri (C54-55), ovary (C56), prostate (C61), testis (C62), kidney (C64-66/C68), bladder (C67), and Hodgkin s disease (C81). They were derived from 21 an cancer registries, grouped into four regions: Northern (Denmark, Finland, Norway, Sweden, Ireland, and the United Kingdom), Western (Austria, France, Germany, The Netherlands, and Switzerland), Southern (Croatia, Italy, Malta, Slovenia, and Spain) and Central (Czech Republic, Lithuania, and Poland). The sources of age-standardized (World Standard Population) incidence, mortality and survival for each country and their coverage are summarised in Table 2. Five-year relative survival estimates were collected from the EUROCARE-3, 7 9 the EUROCARE-4 study, 3 and from a variety of national or regional cancer registry websites or annual reports. Trs in incidence and mortality between 1994 and 2006 (for details, see Table 2) were analyzed by calculating the estimated annual percentage change (EAPC) based on the published age-standardized rates per year, using the Joinpoint Regression Program (version 3.0) from the Surveillance Research Program of the US National Cancer Institute ( If the EAPC was significantly different from zero it was termed an increasing or decreasing tr. The EAPCs for incidence for Switzerland and Lithuania were based on periods and not on annual rates. Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J

4 Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J Table 2 Data sources of cancer incidence, mortality and 5-year relative survival Northern Western Country Serving population of cancer registration (in millions) proportion of national population covered by cancer registration, % Incidence Mortality 5-year relative survival a Period of diagnosis Source Period of death Source Period Source Website Denmark NORDCAN database NORDCAN database 76 Finland NORDCAN database NORDCAN database 76 Finnish Cancer Registry 77 Norway NORDCAN database NORDCAN b Report Cancer in Norway Sweden c Report Cancer Incidence in Sweden Ireland Website National Cancer Registry Ireland 80 UK England & Wales UK Northern Ireland database 76 in Norway Report Cancer NORDCAN database d Website National Cancer Registry Ireland Website Central Statistics Office Ireland 82, Report Patterns of care and survival of cancer patients in Ireland 1994 to WHO mortality Website Cancer e Website National Statistics 84 database 85 Research UK Website National Statistics Website Northern Ireland Cancer Registry f Website Northern Ireland Cancer Registry Report Survival of cancer patients in Northern Ireland UK Scotland Website Scottish Cancer Registry Website Scottish Cancer Registry Website Scottish Cancer Registry 90 Austria (Tyrol) g WHO mortality / Website Tyrol Cancer Registry 91 database Website Tyrol Cancer Registry 91 France h Website French Institute for Public Health Surveillance 92 Germany (Saarland) Report Survie des WHO mortality database 85 patients atteints de cancer en France Website Saarland Gondos, A et al Website Saarland Cancer Registry 94 Cancer Registry 94 Netherlands Website Comprehensive Cancer Centres Netherlands Website Comprehensive Cancer Centres Netherlands Website Comprehensive Centre Amsterdam Website Comprehensive Centre Eindhoven 97 4 E U R O P E A N J O U R N A L O F CA N C E Rxxx (2008) xxx xxx ARTICLE IN PRESS

5 Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J Southern Central Switzerland k Report Cancer in Switzerland (volume 1) 98 Croatia Croatian National Cancer Registry Italy (Modena) Website l WHO mortality database 85 Geneva Cancer 0Registry WHO mortality database Website Modena Report Website Modena Cancer Registry 100 Cancer Registry 100 Cancer in Modena Report Italian cancer figures, report 2007: Survival 102 Malta Website Malta National Cancer Registry m Website Malta National Cancer Registry WHO mortality Reports Cancer WHO mortality Slovenia EUROCIM version database 85 incidence in Slovenia Reports Cancer incidence in Slovenia Spain n EUROCIM 2002 o version database 85 Czech Republic Website Czech National Oncological Register p Website Czech National Oncological Register Report Cancer Incidence 2004 in the 0Czech Republic 108 Lithuania Website Lithuanian WHO mortality Cancer Registry 109 database 85 Poland q EUROCIM WHO mortality version database Website National Cancer Registry Poland Website National Cancer Registry Poland 110 (continued on next page) E U RO P E A N J O U R NA L O F CA N C E Rxxx (2008) xxx xxx 5 ARTICLE IN PRESS

6 6 E U R O P E A N J O U R N A L O F CA N C E Rxxx (2008) xxx xxx Table 2 continued a If available data were used from the EUROCARE-3 7,9 and the EUROCARE-4 project 3. b Data of ovarian, kidney, and bladder cancer from NORDCAN database 76. c Data of corpus uteri, kidney, and bladder cancer from NORDCAN database 76. d Data of oral cavity & pharyngeal, laryngeal, oesophageal, ovarian, testicular, and bladder cancer from WHO mortality database 85. e Only available for England. f Data of laryngeal cancer from the WHO mortality database 85. g Data of stomach, colorectal, lung, breast, and prostate cancer from the Tyrol cancer registry h Data from the FRANCIM network (Bas-Rhin, Calvados, Doubs, Gironde, Haut-Rhin, Hérault, Isère, Loire-Atlantique, Manche, Somme, Tarn, Vée). For cancers of the digestive tract also the specialised registries of Côte-d Or, Saône et Loire, Calvados, Finistère and for haematologic tumours also from Côte-d Or, Gironde and Basse Normandie. The registry of Côte d Or also provided information on gynaecologic and breast cancers. k Used incidence rates are estimates for total Switzerland. l Data of testicular, kidney cancer, and Hodgkin s disease from the report Cancer in Switzerland (volume 2). 116 m Data of oral cavity & pharyngeal, oesophageal, and testicular cancer until 2004 from WHO mortality database 85. n Data from Spanish cancer registries of: Albacete, Asturias, Basque Country, Canary Islands, Cantabria, Catalonia (Tarragona), Cuenca, Girona, Granada, Mallorca, Murcia, Navarra, Zaragoz. o Data of 2002 from Spanish cancer registries of: Catalonia (Tarragona), Girona and Guipúzcoa. p Data of Hodgkin s disease from WHO mortality database 85. q Data from Polish cancer registries of: Lower Silesia (Dolnoslaskie), (Kujawsko-Pomorskie), Lubelskie, Lubuskie, Lodzkie, Malopolskie, Mazowieckie, Opolskie, Podkarpackie, Podlaskie, Pomorskie, Slaskie, Swieto-Krzyskie, Warminsko-Mazurskie, Wielkopolskie, Zachodniopomorskie. Survival trs were analyzed by calculating the relative difference in 5-year relative survival estimates for patients diagnosed between and For cancers of the oral cavity and pharynx, larynx, oesophagus, pancreas, ovary, testis and bladder, survival data were retrieved from literature and individual cancer registries or consortia of cancer registries, because for these tumours data of were not yet available from EUROCARE. A survival tr was determined as an increasing or decreasing tr if the 5-year survival rate changed more than one percent-points in cancers with a poor prognosis (5-year relative survival <20%) and more than two percentpoints in other cancers. 3. Results & comments Results are presented in the accompanying tables, figures and text. Annual incidence and mortality rates per registry are provided on-line, and can be accessed at: publications%2fonline+tables+trs+in++2008%2f Oral cavity and pharyngeal cancer (C00-14). Within incidence among males in the most recent period varied substantially between 5.9 (Finland) and 32 (France) per 100,000. Mortality rates varied considerably less and were highest in countries where incidence was moderate, e.g. in Croatia and Lithuania. Incidence rates among females were highest in Northern and Western and were consistently lower than those for males. The male-to-female ratio decreased during the last 10 years and recently varied between 1.5 and 2.5 in Northern to 7.7 in Lithuania. During the past decade incidence and mortality rates were stable in most an countries, except for a decrease in incidence in Northern and France, Spain, and Slovenia among males, and an increase in incidence among females in some Northern and Western an countries (Table 3a). Fiveyear relative survival rates improved during the past decade in, especially for oro- and nasopharyngeal cancer (Table 3b, 3c). As smoking is one of the main risk factors for these tumours, the observed trs in incidence largely reflect changes in smoking rates, which decreased amongst an males and increased among females in many Southern and Central an countries. For cancers of the oral cavity, alcohol consumption, especially in combination with smoking, is also an important risk factor, as are Epstein-Barr virus and Human papillomavirus infections. 10 Oesophageal cancer (C15). Oesophageal cancer is relatively uncommon in Western societies with varying incidence and mortality patterns during the past decade in. Highest incidence and mortality rates were observed in Ireland and the UK. Rates were low in Southern and Central, especially among females. Increases in incidence and mortality rates were observed among males in Sweden, England, and the Netherlands, and among females in Norway, France and Slovenia. Trs were decreasing in French, German, Slovenian, and Spanish males and in Finnish, Scottish and Croatian females (Table 4a). Five-year relative survival improved or remained stable varying between 7 (Slovenian males) and Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J

7 Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J Table 3a Trs in incidence of and mortality from oral cavity and pharyngeal cancer (C00-14) in by ger Northern Western Southern Central Country Period Incidence Mortality Males Females Males Females Denmark a ()0.8, 1.7) (0.7, 5.4) ()2.0, 3.7) )0.0 ()3.6, 3.7) Finland a )1.5 ()2.7, )0.3) ()1.1, 2.4) ()2.2, 2.3) )2.2 ()4.5, 0.1) Norway a )1.4 ()2.5, )0.3) ()1.7, 2.4) )2.0 ()4.0, 0.0) )3.0 ()6.8, 0.9) Sweden b )0.7 ()1.6, 0.2) ()0.1, 3.1) ()1.4, 2.3) ()2.5, 3.8) Ireland )3.1 ()5.2, )0.9) ()1.2, 3.7) )3.8 ()5.5, )2.0) )1.5 ()4.3, 1.3) UK England (2.0, 3.4) (0.8, 2.3) )0.5 ()1.4, 0.4) )0.2 ()1.3, 1.0) & Wales c UK Northern )2.9 ()4.8, )0.8) )0.6 ()3.4, 2.4) )2.6 ()5.5, 0.4) )1.9 ()7.3, 4.0) Ireland UK Scotland ()0.4, 1.6) ()0.7, 3.4) )1.0 ()2.1, 0.2) )2.2 ()4.3, )0.2) Austria (Tyrol) )0.4 ()7.9, 7.8) )1.5 ()10.1, 7.9) )3.5 ()13.5, 7.6) ()3.0, 15.1) France )1.2 ()1.3, )1.2) (1.2, 2.0) )3.6 ()4.5, )2.7) ()1.1, 2.2) Germany )1.0 ()2.2, 0.3) ()3.1, 5.7) )1.0 ()4.3, 2.4) ()2.3, 7.8) (Saarland) Netherlands )0.3 ()1.6, 1.0) (0.4, 2.6) ()0.6, 1.8) ()0.4, 4.2) Switzerland )1.2 ()7.4, 5.5) ()2.3, 7.0) )1.8 ()3.4, )0.1) ()1.8, 5.3) Croatia )0.1 ()3.8, 3.7) ()1.7, 9.6) )1.8 ()3.6, 0.2) ()3.3, 4.2) Italy )1.0 ()4.4, 2.7) ()6.5, 24.3) )5.5 ()12.2, 1.7) ()4.0, 14.8) (Modena) Malta No data No data )2.4 ()12.9, 9.3) )6.6 ()19.7, 8.7) Slovenia )3.0 ()4.1, )1.9) ()0.1, 8.5) )3.3 ()6.4, )0.1) ()3.8, 9.3) Spain d )6.4 ()8.2, )4.6) )2.7 ()6.0, 0.8) )2.0 ()2.8, )1.2) )0.7 ()2.2, 0.8) Czech (0.0, 1.5) ()0.5, 2.6) ()0.3, 1.5) ()1.8, 2.8) Republic Lithuania ()2.2, 4.5) ()22.7, 37.8) (0.3, 4.2) )0.4 ()4.0, 3.4) Poland )1.1 ()2.2, 0.1) ()0.6, 2.5) )0.6 ()1.3, 0.2) ()1.5, 1.9) a Inclusive C46.2. b Mortality inclusive C46.2. c Incidence only for England. d Incidence data valid for C C Mortality until Mortality until Mortality until Mortality until Mortality until Only average incidence for periods , , and and mortality for Mortality until Only average incidence for periods , , , and * EAPC: estimated annual percentage change, calculated based on the rates during the indicated period. E U RO P E A N J O U R NA L O F CA N C E Rxxx (2008) xxx xxx 7 ARTICLE IN PRESS

8 8 E U R O P E A N J O U R N A L O F CA N C E Rxxx (2008) xxx xxx Table 3b Trs in 5-year relative survival for oral cavity and pharyngeal cancer in a Country Period 5-year relative survival Period 5-year relative survival Tr in survival Males Females Males Females Northern Western UK England & Wales b "/= UK Northern Ireland " UK Scotland b " France c =/" Germany (Saarland) ? Netherlands (Amsterdam) b " Netherlands (Amsterdam) d " Netherlands (Eindhoven) b " Netherlands (Eindhoven) d " Switzerland (Geneva) " Southern Italy (Modena) e " Italy f ? Total oral cavity g h 48.5 " oropharynx g h 39.8 " nasopharynx g h 50.2 " hypopharynx g h 25.5 = a Data reported by individual cancer registries or consortia of cancer registries (sources are shown in Table 1). b Data valid for oral cavity cancer (C01-06). c Data valid for C C d Data valid for pharyngeal cancer (C09-14). e Data valid for head & neck cancer (C01-14, C30-32). f Data valid for head & neck cancer (C01-06, C09-13, C30-32). g Data reported by the EUROCARE-3 study 117. h Data reported by the EUROCARE-4 study 9. Table 3c Overview of recent trs in incidence of, survival for and mortality from oral cavity and pharyngeal cancer in Incidence Survival Mortality Countries Males Females " " = UK-England & Wales France, Netherlands " = = UK-England & Wales "? = Czech Republic Denmark = " = UK-Scotland, Netherlands, Italy UK-Northern Ireland, Switzerland, Italy = " # Switzerland UK-Scotland =? " Lithuania =? = Denmark, Sweden, Austria, Germany, Croatia, Poland # " # UK-Northern Ireland # = # France #? = Finland, Norway #? # Ireland, Slovenia, Spain?? = Malta Malta Finland, Norway, Sweden, Ireland, Austria, Germany, Croatia, Slovenia, Spain, Czech Republic, Lithuania, Poland 23% (Germany), except for Italian and Slovenian males, where survival decreased (Table 4b and 4c). The diverging trs is probably due to geographical variation in the two major subgroups that constitute oesophageal cancer: adenocarcinoma and squamous cell carcinoma and their risk factors. In the Western world, the incidence of adenocarcinoma was mainly rising, while the incidence of squamous cell carcinomas remained stable. 11 Smoking and alcohol consumption are known to be associated with an increased risk of squamous cell carcinoma, while Barrett s oesophagus, largely related to increasing weight and obesity and resulting reflux, is an important risk factor for adenocarcinoma. 12 Modest improvements in survival seem to have occurred during the last decade, most likely related to the increased incidence of adenocarcinoma and the increasing regionalization of surgery. 13,14 The decreases in survival among Italian and Slovenian males are probably due to increasing completeness of data. Stomach cancer (C16). Incidence and mortality rates of stomach cancer varied considerably within, being Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J

9 Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J Table 4a Trs in incidence of and mortality from oesophageal cancer (C15) in by ger Northern Western Southern Central Country Period Incidence Mortality Males Females Males Females Denmark ()0.0, 2.9) ()1.0, 3.1) (0.3, 3.9) ()2.4, 6.6) Finland ()1.3, 1.9) )2.6 ()4.7, )0.5) )0.1 ()2.1, 2.0) )2.6 ()5.7, 0.7) Norway ()0.4, 4.6) (0.2, 5.5) ()1.5, 3.8) ()0.5, 6.9) Sweden (0.8, 2.9) ()2.5, 2.8) ()0.4, 3.6) ()0.4, 4.4) Ireland ()1.3, 2.1) )0.9 ()2.3, 0.6) )0.8 ()2.3, 0.9) )1.9 ()4.2, 0.5) UK England (1.0, 1.6) )0.3 ()1.1, 0.5) (0.3, 0.9) )0.5 ()1.0, 0.1) & Wales a UK Northern )0.9 ()3.6, 2.0) )2.0 ()5.0, 1.1) ()1.5, 2.1) )1.7 ()3.7, 0.4) Ireland UK Scotland ()0.5, 1.1) )1.8 ()3.3, )0.2) ()0.5, 0.7) )1.7 ()3.1, )0.3) Austria (Tyrol) ()8.1, 9.5) )1.0 ()14.6, 14.9) ()10.4, 12.5) )13.9 ()31.2, 7.7) France )2.6 ()2.8, )2.5) (1.5, 3.6) )3.4 ()4.1, )2.6) ()0.2, 2.4) Germany )2.6 ()4.3, 1.0) ()1.5, 7.4) )0.7 ()2.8, 1.4) ()1.8, 16.3) (Saarland) Netherlands (2.0, 4.0) ()0.9, 2.3) (0.6, 3.0) ()0.9, 2.1) Switzerland ()7.2, 9.3) )0.0 ()12.6, 14.4) )0.2 ()1.7, 1.3) )1.1 ()4.4, 2.2) Croatia )2.1 ()4.1, )0.1) )5.3 ()10.3, 0.1) )1.2 ()4.0, 1.6) )5.0 ()7.2, )2.7) Italy (Modena) )0.7 ()8.0, 7.1) ()7.6, 17.6) )1.5 ()7.7, 5.3) )3.0 ()16.0, 12.0) Malta No data No )9.1 ()16.8, )0.7) )9.7 ()21.1, 3.4) data Slovenia )2.0 ()4.1, 0.2) (2.4, 7.7) )5.0 ()9.0, )0.6) ()5.2, 12.4) Spain )1.5 ()11.3, 9.5) ()7.8, 17,4) )2.2 ()2.7, )1.6) ()0.8, 2.7) Czech )0.1 ()1.9, 1.8) ()2.6, 5.6) )0.4 ()1.7, 1.0) ()1.8, 7.9) Republic Lithuania ()2.0, 4.4) )3.4 ()14.4, 9.0) ()0.4, 3.3) )1.6 ()6.0, 3.1) Poland )0.1 ()0.8, 0.6) )2.2 ()4.4, 0.1) ()1.1, 0.8) )0.9 ()2.6, 0.9) a Incidence only for England. 1 Mortality until Mortality until Mortality until Mortality until Mortality available until Only average incidence for periods , , and and mortality for Mortality until Only average incidence for periods , , , and * EAPC: estimated annual percentage change, calculated based on the rates during the indicated period. E U RO P E A N J O U R NA L O F CA N C E Rxxx (2008) xxx xxx 9 ARTICLE IN PRESS

10 10 E U R O P E A N J O U R N A L O F CA N C E Rxxx (2008) xxx xxx Table 4b Trs in 5-year relative survival for oesophageal cancer in a Country Period 5-year relative survival Period 5-year relative survival Tr in survival Males Females Males Females Northern Western Southern Finland ? Norway " UK England & Wales = UK Northern Ireland " UK Scotland "/= France = Germany (Saarland) ? Netherlands (Amsterdam) = Netherlands (Eindhoven) b = Switzerland (Geneva) = Italy (Modena) "/# Italy ? Slovenia "/# Total c d 12.3 " a Data reported by individual cancer registries or consortia of cancer registries (sources are shown in Table 1). b 3-year relative survival. c Data reported by the EUROCARE-3 study 117. d Data reported by the EUROCARE-4 study 9. Table 4c Overview of recent trs in incidence of, survival for and mortality from oesophageal cancer in Incidence Survival Mortality Countries Males Females " = " UK-England & Wales, Netherlands " = = France " # = Slovenia "? = Sweden Norway = " = Norway, UK-Northern UK-Northern Ireland Ireland/Scotland, Italy = " # Slovenia = = = Switzerland UK- England & Wales, Netherlands = # = Italy =? " Denmark ) =? = Finland, Ireland, Austria, Czech Republic, Lithuania, Poland =? # Spain Croatia # " # UK-Scotland # = # France ) #? = Germany, Croatia Finland Denmark, Sweden, Ireland, Austria, Germany, Switzerland, Spain, Czech Republic, Lithuania, Poland generally higher in Southern and Central and always twice as high in males compared with females. In most an countries, incidence and mortality rates have been dropping, while 5-year relative survival slowly improved (Table 5a and 5b, Fig. 3). A combination of improved methods of fresh food preservation with higher vitamin C content and reduced salting, 15 decreased smoking prevalence and, more importantly, decreasing infection rates of Helicobacter Pylori, 16 has probably resulted in the observed decreases in incidence and, subsequently, mortality. Contrary to the downward trs for non-cardia cancers, incidence rates for cancers of the cardia, initially representing less than 20% of all gastric cancers, have been reported to increase or remain stable. 17,18 Differences in gastric cancer survival are largely related to age, subsite and histological type, with few changes over time 19 regardless of the country. On one hand the shift from the pylorus to the cardia has negative implications for survival because of the worse prognosis of cardia tumours. This may be countered however, by earlier detection due to larger availability of oscopy, especially when followed by adequate surgery. 20 Colorectal cancer (C18-21). Incidence of colorectal cancer among males increased modestly in most countries and markedly in Austria, Croatia, Slovenia, Spain, and the Czech Republic. Among females, the incidence rates were stable with some decreases in Scotland, Northern Ireland, and Poland, contrasting a clear increase in Spain. The male- Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J

11 Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J Table 5a Trs in incidence of and mortality from stomach cancer (C16) in by ger Northern Western Southern Central Country Period Incidence Mortality Males Females Males Females Denmark )2.3 ()3.4, )1.2) )1.8 ()4.4, 0.9) )4.1 ()6.7, )1.4) )3.7 ()7.1, )0.1) Finland )4.3 ()5.3, )3.3) )4.0 ()4.9, )3.1) )4.6 ()5.4, )3.7) )2.9 ()4.4, )1.3) Norway )4.3 ()5.4, )3.3) )2.9 ()4.3, )1.6) )4.8 ()6.5, )3.0) )4.9 ()6.4, )3.4) Sweden )3.1 ()3.8, )2.4) )2.9 ()4.1, )1.6) )3.5 ()4.2, )2.7) )2.6 ()3.7, )1.5) Ireland )2.6 ()3.2, )1.9) )1.7 ()2.5, )0.9) )4.5 ()5.5, )3.6) )4.8 ()6.6, )3.0) UK England )4.1 ()5.0, )3.2) )3.4 ()4.1, )2.7) )4.8 ()5.2, )4.4) )4.0 ()4.6, )3.4) & Wales a UK Northern )4.0 ()6.2, )1.8) )2.7 ()4.4, )1.1) )3.9 ()6.0, )1.8) )2.4 ()4.8, 0.1) Ireland UK Scotland )3.2 ()4.0, )2.5) )3.7 ()4.6, )2.7) )3.3 ()4.0, )2.7) )4.4 ()6.1, )2.7) Austria (Tyrol) )4.5 ()7.2, )1.7) )3.5 ()5.9, )1.1) )7.3 ()8.7, )5.9) )4.9 ()7.9, )1.9) France )2.2 ()2.4, )2.0) )2.7 ()2.7, )2.6) )2.7 ()3.1, )2.2) )2.4 ()2.8, )1.9) Germany )1.8 ()2.6, )1.0) )3.8 ()5.7, )1.9) )3.7 ()5.9, )1.6) )4.7 ()5.8, )3.6) (Saarland) Netherlands )3.8 ()4.3, )3.3) )2.3 ()3.4, )1.1) )4.4 ()5.1, )3.6) )2.8 ()4.2, )1.4) Switzerland )3.0 ()12.9, 8.0) )2.6 ()14.5, 10.9) )4.4 ()5.7, )3.2) )4.9 ()5.7, )4.0) Croatia )3.0 ()5.2, )0.9) )2.6 ()4.3, )0.8) )2.8 ()4.6, )1.1) )3.0 ()4.1, )1.8) Italy (Modena) )4.4 ()6.6, )2.2) )4.0 ()6.8, )1.1) )5.0 ()8.4, )1.5) )5.9 ()8.6, )3.2) Malta )2.9 ()7.6, 2.2) )2.4 ()5.7, 0.9) )5.1 ()7.7, )2.3) )1.4 ()5.8, 3.2) Slovenia )2.9 ()4.1, )1.8) )3.6 ()4.9, )2.3) )4.2 ()6.2, )2.3) )4.7 ()6.8, )2.5) Spain )3.1 ()6.4, 0.4) ()4.7, 5.4) )3.7 ()4.1, )3.3) )3.8 ()4.5, )3.1) Czech Republic )3.9 ()4.6, )3.2) )3.9 ()4.6, )3.2) )4.8 ()5.5, )4.1) )4.5 ()5.1, )3.8) Lithuania )2.1 ()3.3, )0.9) )1.4 ()11.4, 9.7) )3.0 ()3.7, )2.3) )2.5 ()3.6, )1.4) Poland )5.8 ()7.0, )4.5) )5.4 ()6.7, )4.2) )3.2 ()3.5, )2.9) )3.2 ()3.6, )2.8) a Incidence only for England. 1 Mortality until Mortality until Mortality until Mortality until Mortality until Only average incidence for periods , , and and mortality for Mortality until Only average incidence for periods , , , and * EAPC: estimated annual percentage change, calculated based on the rates during the indicated period. E U RO P E A N J O U R NA L O F CA N C E Rxxx (2008) xxx xxx 11 ARTICLE IN PRESS

12 12 E U R O P E A N J O U R N A L O F CA N C E Rxxx (2008) xxx xxx Relative change in 5-year relative survival rates (%) Denmark Finland Norway Sweden Ireland UK England UK Wales UK Northern Ireland UK Scotland Austria France Germany Netherlands Switzerland Italy Malta Slovenia Spain Czech Republic Poland Total year relative survival rate relative change Fig. 3 Trs in 5-year age-adjusted relative survival for stomach cancer in Sources: EUROCARE-3 7 and EUROCARE-4. 3 Table 5b Overview of recent trs in incidence of, survival for and mortality from stomach cancer in Incidence Survival Mortality Countries Males Females = " # Spain Spain = = # Switzerland Switzerland =? = Malta =? # Malta Denmark, Lithuania # " = UK-Northern Ireland a # " # Finland, Norway, Sweden, UK a, Germany, Italy, Slovenia, Poland Finland, Norway, Sweden, UK-England & Wales/Scotland, Germany, Italy, Slovenia, Poland # = # Netherlands Netherlands # # # Austria, France Austria, France #? # Denmark, Ireland, Croatia, Czech Republic, Lithuania Ireland, Croatia, Czech Republic a Survival trs of UK-Northern Ireland are based on a report of the North-Ireland Cancer Registry 89. to-female ratio remained stable at 1.5. Mortality rates decreased across but remained very high in Denmark, Norway, and Ireland in comparison with other Northern and Western an countries (Table 6a). Five-year relative survival increased, especially in Poland, Slovenia, and the Czech Republic (Fig. 4, Table 6b). The increasing incidence rates may be due to a relatively late, but rapid transition towards a life style being increasingly rich in sugar, red and processed meat, poor in fiber consumption and physical activity, resulting in increasing body mass index Improvement of survival, especially in younger patients, is probably due to positive changes in detection and treatment of colorectal cancer since the mid 1990s. This includes a widespread availability of oscopy, either or not as part of screening activities, Total Mesorectal Excision (TME) surgery for rectal cancer, and more widespread use of (pre-operative) radiotherapy The high mortality rate in some Northern an countries is possibly caused by Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J

13 Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J Table 6a Trs in incidence of and mortality from colorectal cancer (C18-21) in by ger Northern Western Southern Central Country Period Incidence Mortality Males Females Males Females Denmark (0.4, 1.7) ()0.7, 1.1) )1.8 ()2.8, )0.8) )0.0 ()1.7, 1.7) Finland ()0.0, 1.2) ()0.1, 1.1) )1.1 ()1.9, )0.2) )1.1 ()2.2, )0.1) Norway (0.5, 1.5) ()0.0, 0.7) )0.8 ()1.4, )0.2) )1.0 ()2.2, 0.2) Sweden (0.1, 0.9) (0.2, 1.3) )0.4 ()1.0, 0.3) )0.7 ()1.3, )0.2) Ireland )0.0 ()0.5, 0.5) ()0.6, 0.9) )1.7 ()2.9, )0.6) )2.3 ()3.9, )0.7) UK England )0.2 ()0.8, 0.4) )0.5 ()1.3, 0.3) )2.1 ()2.3, )1.8) )2.3 ()2.7, )1.9) & Wales a UK Northern )0.4 ()1.6, 0.8) )1.6 ()2.5, )0.7) )1.2 ()3.0, 0.6) )2.3 ()4.0, )0.5) Ireland UK Scotland b ()0.8, 0.8) )0.9 ()1.8, )0.1) )1.7 ()2.1, )1.3) )2.7 ()3.4, )2.0) Austria (Tyrol) (0.0, 4.7) ()0.3, 2.6) )1.0 ()7.3, 5.7) )1.3 ()4.0, 1.5) France (0.6, 0.7) (0.3, 0.5) )0.6 ()1.3, )0.0) )1.0 ()1.7, )0.2) Germany ()0.4, 1.1) )0.1 ()0.9, 0.8) )2.3 ()2.8, )1.9) )3.1 ()4.8, )1.4) (Saarland) Netherlands (0.5, 1.3) (0.3, 1.3) )0.7 ()1.3, )0.0) )1.1 ()1.7, )0.5) Switzerland ()1.7, 2.4) ()0.7, 1.5) )2.4 ()3.2, )1.5) )1.6 ()2.6, )0.6) Croatia (0.1, 5.2) ()0.3, 5.2) ()0.4, 4.4) ()1.3, 2.5) Italy (Modena) ()0.2, 2.3) ()1.1, 3.5) )1.9 ()3.8, )0.0) )1.2 ()4.4, 2.1) Malta b ()1.5, 3.4) )0.9 ()3.6, 1.9) )3.1 ()5.1, )0.9) )0.1 ()2.0, 1.9) Slovenia (1.9, 3.4) ()0.0, 2.1) ()1.1, 2.1) )2.1 ()3.9, )0.3) Spain (0.1, 9.0) (0.5, 6.5) (0.6, 1.3) )1.0 ()1.4, )0.6) Czech Republic (0.4, 1.8) ()0.3, 0.9) )0.8 ()1.6, )0.0) )1.1 ()1.7, )0.4) Lithuania ()2.2, 6.2) ()12.6, 20.7) ()0.2, 1.2) )1.2 ()2.2, )0.3) Poland )0.2 ()1.6, 1.3) )1.1 ()2.2, )0.0) (1.3, 2.0) ()0.7, 1.0) a Incidence only for England. b Data valid for C Mortality until Mortality until Mortality until Mortality until Mortality until Only average incidence for periods , , and and mortality for Mortality until Only average incidence for periods , , , and * EAPC: estimated annual percentage change, calculated based on the rates during the indicated period. E U RO P E A N J O U R NA L O F CA N C E Rxxx (2008) xxx xxx 13 ARTICLE IN PRESS

14 14 E U R O P E A N J O U R N A L O F CA N C E Rxxx (2008) xxx xxx Relative change in 5-year relative survival rates (%) Denmark Finland Norway Sweden Ireland UK England UK Wales UK Northern Ireland UK Scotland Austria France Germany Netherlands Switzerland Italy Malta Slovenia Spain Czech Republic Poland Total year relative survival rate relative change Fig. 4 Trs in 5-year age-adjusted relative survival for colorectal cancer in Sources: EUROCARE-3 9 and EUROCARE-4. 3 Table 6b Overview of recent trs in incidence of, survival for and mortality from colorectal cancer in Incidence Survival Mortality Countries Males Females " " " Spain ) " " = Austria, Slovenia ) " " # Norway, France, Netherlands, France, Netherlands, Spain Czech Republic "? = Croatia "? # Denmark ) = " " Poland ) = " = UK-Northern Ireland Norway, Austria, Italy, Malta = " # Finland, Ireland a, UK-England & Wales/Scotland, Germany, Switzerland, Italy, Malta Finland, Ireland a, UK-England & Wales, Germany, Switzerland, Slovenia, Czech Republic =? = Lithuania Denmark, Croatia =? # Lithuania # " = Poland # " # UK-Northern Ireland/Scotland a Survival trs are based on a report of the Ireland Cancer Registry 81. deficient access to oscopic care, and less effective patient management. 27 Pancreatic cancer (C25). Incidence and mortality rates of pancreatic cancer were similar across and quite stable over time. However, in Denmark and France, incidence and mortality increased, and they decreased in Sweden and Poland (Table 7a). Rates were higher among males than females (male-to-female ratio 1.5). Five-year relative survival remained very low varying between 2 and 8% (Table 7b and 7c). Pancreatic mortality rates have increased throughout between the late 1950s and the 1980s among males, and the 1990s among females followed by a leveling off which is Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J

15 Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J Table 7a Trs in incidence of and mortality from pancreatic cancer (C25) in by ger Northern Western Southern Central Country Period Incidence Mortality Males Females Males Females Denmark (0.9, 3.2) (0.2, 3.6) ()2.7, 3.4) ()0.7, 3.8) Finland ()1.0, 1.2) ()0.4, 1.9) ()0.8, 1.4) ()0.6, 2.6) Norway )0.1 ()1.0, 0.8) )0.3 ()1.5, 0.9) ()1.2, 1.4) ()1.0, 1.6) Sweden )2.2 ()3.4, )0.9) )1.3 ()2.4, )0.3) )0.4 ()1.3, 0.4) )0.2 ()1.0, 0.6) Ireland )0.0 ()1.3, 1.2) )0.4 ()2.0, 1.3) )1.5 ()2.8, )0.1) ()1.2, 1.8) UK England )0.2 ()0.6, 0.3) ()0.7, 1.4) )0.2 ()0.6, 0.2) ()0.1, 1.2) & Wales a UK Northern ()2.8, 4.0) ()2.8, 3.4) )0.4 ()2.7, 2.1) ()2.0, 2.8) Ireland UK Scotland )1.0 ()2.5, 0.6) )0.1 ()1.6, 1.4) )0.3 ()1.3, 0.7) ()0.9, 1.3) Austria (Tyrol) ()6.5, 7.3) ()5.6, 9.6) )2.2 ()6.8, 2.6) (2.5, 11.2) France (0.9, 1.4) (1.4, 2.4) (0.1, 1.3) (1.1, 2.4) Germany ()0.3, 5.6) ()1.2, 4.4) ()1.1, 3.1) ()2.5, 2.7) (Saarland) Netherlands )1.0 ()2.6, 0.6) )1.0 ()2.3, 0.4) )0.5 ()1.5, 0.5) ()0.6, 1.2) Switzerland ()5.0, 6.0) )0.8 ()3.3, 1.7) )0.1 ()0.7, 0.5) )0.5 ()1.9, 1.0) Croatia ()1.5, 2.5) ()1.4, 4.2) ()1.9, 3.3) ()1.3, 4.2) Italy (Modena) ()2.0, 5.0) )0.8 ()4.6, 3.2) )1.1 ()4.0, 2.0) )1.5 ()2.7, )0.2) Malta )1.5 ()5.6, 2.8) ()4.0, 8.2) )3.1 ()6.3, 0.2) ()2.0, 3.3) Slovenia ()2.2, 4.6) ()1.6, 5.6) ()0.2, 2.4) ()2.0, 5.2) Spain ()5.2, 10.0) ()2.3, 6.3) (0.7, 1.9) ()0.2, 1.9) Czech Republic )0.0 ()1.0, 0.9) ()0.6, 1.2) )0.7 ()1.6, 0.2) )0.2 ()0.8, 0.5) Lithuania )1.4 ()7.4, 5.1) )0.2 ()10.2, 10.9) )0.6 ()1.5, 0.4) )0.6 ()2.2, 1.0) Poland )3.9 ()5.4, )2.4) )4.2 ()6.4, )1.8) )0.1 ()0.6, 0.4) ()0.4, 0.5) a Incidence only for England. 1 Mortality until Mortality until Mortality until Mortality until Mortality until Only average incidence for periods , , and and mortality for Mortality until Only average incidence for periods , , , and * EAPC: estimated annual percentage change, calculated based on the rates during the indicated period. E U RO P E A N J O U R NA L O F CA N C E Rxxx (2008) xxx xxx 15 ARTICLE IN PRESS

16 16 E U R O P E A N J O U R N A L O F CA N C E Rxxx (2008) xxx xxx Table 7b Trs in 5-year relative survival for pancreatic cancer in by ger a Country Period 5-year relative survival Period 5-year relative survival Tr in survival Males Females Males Females Northern Western Southern Central Finland ? Norway = UK England & Wales = UK Northern Ireland = UK Scotland = France "/= Germany ? (Saarland) Netherlands " (Amsterdam) Netherlands (Eindhoven) b # Italy (Modena) = Italy ? Slovenia ? Czech Republic ? Total c d 5.5 " a Data reported by individual cancer registries or consortia of cancer registries (sources are shown in Table 1). b 3-year relative survival. c Data reported by the EUROCARE-3 study 117. d Data reported by the EUROCARE-4 study 9. Table 7c Overview of recent trs in incidence of, survival for and mortality from pancreatic cancer in Incidence Survival Mortality Countries Males Females " " " France " = " France "? = Denmark Denmark = = = Norway, UK, Netherlands, Italy Norway, UK, Netherlands = = # Italy =? " Spain Austria =? = Finland, Austria, Germany, Switzerland, Croatia, Malta, Slovenia, Czech Republic, Lithuania =? # Ireland #? = Sweden, Poland Sweden, Poland Finland, Ireland, Germany, Switzerland, Croatia, Malta, Slovenia, Spain, Czech Republic, Lithuania confirmed by our data. 28 This leveling off is partly due to the decline in smoking which is the main risk factor for pancreatic cancer. 15,29,30 Factors related to obesity, such as type 2 diabetes and high blood glucose levels 31 also seem to be important risk indicators, as well as occupational exposures to pesticides or dyes. 32,33 Previously postulated associations with coffee and alcohol consumption were not confirmed. 34 No major improvements in treatment have occurred, causing the survival rates to remain stable. Centralization of surgery may contribute to future improvement in survival of pancreatic cancer. Laryngeal cancer (C32). Incidence and mortality rates of cancer of the larynx varied considerably throughout, especially among males. Lowest rates were observed in the Scandinavian countries, except in Denmark, and highest rates in Southern and Central (Table 8a). This cancer was 4 (Scotland) to 49 (Spain) times more common among males than females. In all an regions, both incidence and mortality rates declined over the past decade, especially among males, for incidence more markedly in Northern, and mortality in Southern. However, in most countries, 5-year relative survival did not show marked improvements, except for Northern Irish, Scottish and Swiss males (Table 8b and 8c). The most important environmental risk factors are smoking and alcohol consumption. 35,36 The relative risks of smokers seem to be higher for supraglottic than glottic cancer, which is in accordance with the anatomical location of supraglottic tissue, being more readily exposed to tobacco smoke than the other laryngeal subsites. The decreasing smoking Please cite this article as: Henrike E. Karim-Kos et al., Recent trs of cancer in : A combined approach of..., Eur J